Abstract
The mammalian SWI/SNF, or BAF complex, has a conserved and direct role in antagonizing polycomb-mediated repression. Yet, BAF appears to also promote repression by polycomb in stem cells and cancer. How BAF both antagonizes and promotes polycomb-mediated repression remains unknown. Here, we utilize targeted protein degradation to dissect the BAF-polycomb axis in embryonic stem cells on the timescale of hours. We report that rapid BAF depletion redistributes both PRC1 and PRC2 complexes from highly occupied domains, like Hox clusters, to weakly occupied sites that are normally opposed by BAF. Polycomb redistribution from highly repressed domains results in their decompaction, gain of active epigenomic features, and transcriptional derepression. Surprisingly, through dose-dependent degradation of PRC1 & PRC2 we identify both a conventional role for BAF in polycomb-mediated repression and a second mechanism acting by global redistribution of polycomb. These findings provide new mechanistic insight into the highly dynamic state of the Polycomb-Trithorax axis.
Competing Interest Statement
The authors have declared no competing interest.
